The capacity of the ventricles to perform work (i.e., power) is essential for moving blood throughout the circulatory system. Ventricular/myocyte power is determined ultimately by three myofibrillar properties; (i) the amount of force developed, (ii) the rate of force development, and (iii) the rate that myocardium shortens against loads. However, the sub-cellular processes that determine these properties are incompletely understood. The overall purpose of this study is to determine the sub-cellular factors that regulate myocyte power generating capacity. The specific objectives of the proposed studies are designed to determine (1) if PKA-mediated phosphorylation of cardiac troponin I (cTnI) is both necessary and sufficient to dictate sarcomere length dependence of force generation in cardiac myocytes, (2) how titin, MyBP-C, and myosin cross-bridges interact to modulate sarcomere length dependence of power output, and (3) to determine the time-course of changes in sarcomere length dependence of force, rates of force development, loaded shortening, and power output during the progression of heart failure. A rodent model of heart failure will be used to test the hypothesis that myocytes in compensated hearts exhibit greater sarcomere length dependence of force and power output due to a combination of greater expression of the larger N2BA titin isoform and greater PKA- induced myofibrillar protein phosphorylation, but with progression to ventricular failure sarcomere length dependence of force and power is markedly reduced due to reduced PKA- mediated phosphorylation of titin, MyBP-C, and cTnI. These studies are highly significant in their potential to determine the basis for the control of power-generating capacity in healthy myocytes and how these processes are altered with the progression of heart failure.